The candidate obtained his MD and PhD in Immunology from New York University, with Dr. Jeanette Thorbecke. He then moved to the Children's Hospital, Boston, for residency in Pediatrics and a fellowship in Allergy/Immunology with Dr. Raif S. Geha. In 1986, he moved to Stanford University, as an Assistant Professor of Pediatrics. The academic environment at Stanford is outstanding in basic science immunology, where the candidate is in the Pediatric Allergy/Pulmonary Division. He is a member of the Immunology Program Faculty and has an Immunology Program graduate student in the lab. In addition, the candidate participates in the MacArthur Program Project in the Molecular Biology of Parasites at Stanford, which supports a postdoc in the lab. The career goals of the candidate are to establish his lab as a leader in the analysis of CD4+ T cell heterogeneity, especially as it relates to regulation of allergic diseases. In addition, he wishes to further expand the clinical program in Allergy/Immunology at Stanford. The proposed research project is already underway, and involves the examination of human CD4+ T cell subsets with restricted cytokine profiles. The division of CD4+ T cells into subsets is of fundamental importance in the regulation of isotype specific responses and in the regulation of responses to different types of antigens. Activation of CD4+ T cell subsets with inappropriate cytokine profiles may result in the development of allergic or autoimmune disease, or susceptibility to specific types of infection. The existence of CD4+ T cell subsets, though well established in mice, has not been well studied in man. The purpose of this proposal is to: 1. define the subtypes of human CD4+ T cell clones, and to determine under what conditions each subtype is preferentially stimulated. 2. examine how these subtypes of T cell clones regulate isotype specific responses in B cells. 3. determine how CD4+ T cell subsets may be involved in the pathogenesis of allergic disease. To study these problems, the candidate has developed exceptional culture techniques for generating and studying CD4+ clones. In addition, he has enlisted the support of other investigators to help apply molecular biology techniques to the analysis of his clones, and to provide a large number of valuable reagents necessary to evaluate the cellular interactions involved in the regulation of cytokine synthesis.